Parthenium integrifolium (L.) (family Asteraceae), also commonly known as Missouri snake root, grows wild in woodland and prairies of North America. The herb is 30-130 cm high with numerous white flowerheads forming a flat inflorescence up to 25 cm wide. The root is comprised of a short, conical or bulbshaped headstem that has a diameter of up to 4 cm and elongated secondary, twisted branches leading from the headstem.
A number of chemicals have been identified as major components of Parthenium integrifolium extracts. One group are the sesquiterpene lactones represented by tetraneurin E and tetraneurin C. Another group are the sesquiterpene esters represented by echinadiol cinnamate, epoxy echinadiol cinnamate, echinaxanthol cinnamate and dihydroxynardol cinnamate. Yet another group are the flavonoids represented by quercetagetin methyl ethers and their O-glycosides. Another characteristic component of Parthenium integrifolium is pyromeconic acid. Other chemicals present in the plant are coumarins and diverse phenolic glycosides.
The German patent application, publication no. 36 38 715 A1 describes the above mentioned sesquiterpene esters derived from Parthenium integrifolium. According to the experimental section of that application, immunological activity tests of the sesquiterpene esters showed that they enhanced granulocyte phagocytosis in vitro up to 30%. This effect is to be considered a pro-inflammatory action related to the non-specific part of the immune system (the reticuloendothelial phagocytic system).
At present the nonsteroidal antiinflammatory drugs (NSAIDS) are the most commonly applied therapeutic agents for the treatment of conditions associated with inflammation and pain. The NSAIDs exert their action by inhibiting the prostaglandin-generating enzyme cyclooxygenase (COX). There are two biochemical subtypes of cyclooxygenase denominated COX-1 and COX-2. COX-1 is constitutively expressed in most cells and is responsible for the formation of prostaglandins which mediate important basic physiological functions, e.g. providing an intact mucosa in the ventricle. COX-2 is not normally present, but may be induced by certain serum factors, cytokines and growth factors and responsible for the formation of inflammatory prostaglandins which mediate many symptoms of inflammation. The NSAIDs are generally non-selective, meaning that they inhibit both COX-2 and COX-1 resulting in an antiinflammatory and pain relieving effect due to the inhibition of COX-2 and a number of side effects due to the inhibition of COX-l, of which gastric ulceration is one of the most important.
Autoimmune disorders like multiple sclerosis, morbus Crohn, rheumatoid arthritis, diabetes mellitus, etc. are associated with an overactivation of the inflammatory arm of the immune system (T.sub.H 1 pathway) leading to well known symptoms and serious tissue destruction. The most well established treatment for these disorders is the management of corticosteroids which exert their action by non-selectively inhibiting the function and proliferation of different types of immune cells. Unfortunately the corticosteroids are associated with a number of serious side effects e.g. immuno-suppression and osteoporosis.